earlier tonight I was listening to twiv from the 16th, and they also covered this weird Spike protein paper. I really appreciate your write up, because it took them about half an hour or to explain but the reason they were covering something for which they were scratching their heads as to why the experiment was done in the first place given that it had no relation to anything real life was because anti-vaxxers were latching on to it.
I see nothing in this case report connecting the inflammatory symptoms in this person (an 18 year old man who is for some reason described as a "boy") have anything to do with vaccination. 10 weeks from vaccination until the appearance of symptoms? Come on. That would mean that out of >1 billion people who have received mRNA vaccines at this point, this is the first person to have a new symptom more than 6 weeks after vaccination.
The much more likely scenarios are either (1) MIS-C is a misdiagnosis or (2) the COVID-19 negative test was a false negative. I find it odd that the case report is lacking in detail, too--they say he presented only with a fever, but was given antibiotics for "suspected pneumonia"? Was the stethoscope not available that day? The treating physician must have had more reason than simple temperature to begin empirical treatment.
This means that (1) has a lot of options here; generalized and unexplained inflammation along with suspected pneumonia? This sounds like a situation where this patient experienced an infection, and that infection led to all of these symptoms in some way or another. I do not see any reason to connect this with a vaccination that occurred 2.5 months earlier when nothing like that has ever happened to anyone else who got this vaccination.
Given that COVID-19 is everywhere, (2) is also a strong possibility.
The idea that the most likely explanation is a connection with the vaccine is just ludicrous.
CDC definition also calls the border line for MIS-C the age of 21, but I think the term "boy" is rather inappropriate here. "Adolescent" might have been OK.
Eh, the WHO definition covers ages 0-19. Maybe time to just start calling it MIS?
Interestingly, though near-totally unrelatedly, in Germany (where this case report originated), the justice system treats people are juveniles until age 25.
How do nonsense conclusions like this pass peer review? This isn't the first egregiously overstepping conclusion I've seen by far, but it's probably one of the worst.
Well, let me tell you a story. I was in a lab once that was a regular peer reviewing lab for oncology papers. One day a paper came in that the PI decided wasn't worth his time, and he said he was going to send back a bad review unless his senior postdoc disagreed with his thinking that the paper was half-baked and under-developed. This was around 4 PM. The postdoc turned to me after the PI left and said, "Well, the future of this paper now depends on how tired I am today." Basically, the peer review process there was turning on a snap judgment and an exhausted and underpaid person.
I think of that story every time I see a problem with peer review, even though the situation is sort of opposite to what we see here. Peer reviewers are unpaid and overworked and sometimes--often?--come to hasty conclusions because they are not able to give the work they're assigned the attention that it is due.
However, the (academic) editor who worked on this is intended to be a second line of defense. Editors can ask for changes just as much as peer reviewers can. Editors should ask for changes to conclusions that are unsupported and likely to be inflammatory. Here, the editor didn't. I imagine because that person is underpaid, overworked, and wasn't paying great attention.
Academic publishing is pretty broken, because it grew out of a system of rich European nobles writing letters to each other, and hasn't become much more lucrative than how it started off. Peer review is a huge unpaid time sink, editing isn't much better, and despite enormous fees to publish and to subscribe, journals generally don't make very good margins. It's a problem to which I have no solutions, though I am sure there are smarter people than myself giving this attention.
MDPI has a reputation as a predatory publisher with an inadequate peer review process. They were on Jeffrey Beall's list of predatory publishers for a while; they were removed, but he later said this was due to pressure from his employer, and he continues to call them a predatory publisher elsewhere (e.g., on Twitter).
Now, a predatory journal is not quite the same thing as a pseudojournal, and I don't think anything appearing in an MDPI publication should necessarily be disregarded. Sometimes legit research appears on such publications because, e.g., the authors have been misled. But I do think such publishers in general, and MDPI in particular, have shown that what they publish warrants a higher-than-usual degree of scrutiny.
The first question I ask myself when these sorts of articles come out is: who are the authors? Do they actually have relevant expertise? Have they been active in peddling misinformation, conspiracies, pseudoscience?
I typically evaluate it based on the journal rather than the publisher, since there can be a lot of variation at the journal level. I've heard of Viruses before, and it has had some meaningfully valuable research in it before. This is not one of those cases.
Certainly going forward I'm going to be more skeptical than I was before.
That makes sense re: basing it on the journal rather than the publisher. In the case of Vaccines, though, I have to wonder whether the apparent far-right sympathies of MDPI's sole owner (see: https://forbetterscience.com/2020/12/29/mdpi-and-racism/) is playing a role here. (Anti-vaccine sentiment isn't the exclusive province of the far right, of course, but I think it's fair to say the two have found some... synergy during the pandemic.)
Yeah, this paper I have heard of before. It is highly suspect and there have been retraction calls. The journal Vaccines has had a surprising number of these nonsensical antivaccine papers during the pandemic. This is one of the situations where I must look at the journal and say that it's not a good one.
You wrote, "Lastly, it just doesn’t seem possible for spike protein to be getting into the right place to do this. The mRNA and adenovirus-vector vaccines are all sent right into the muscle. They don’t go anywhere near the bone marrow and they don’t produce spike proteins in a way that it seems possible for those products to get into bone marrow or the thymus."
How about the non-US-approved vaccines, e. g. all the Chinese ones, that are either inactivated virus or protein subunit? I'm actually pretty sure neither one could introduce spike into the nucleus (where DNA replicates in mammalian cells) but you're the expert. Certainly spike can bind to the cell membrane, but does it pass the nuclear membrane?
You refer to a "protected compartment" (meaning the bone marrow), but at the cellular level the nucleus is also a protected compartment.
I think the key point is that infection introduces orders of magnitude more spike protein into a person's body than any vaccination, attached to actual virions.
The nuclear localization issue is pretty weird, I will agree with you. It's a bit of a head-scratcher. I have never heard anything about spike having a nuclear localization signal in its sequence. I don't know how it would get into the nucleus, either. I wasn't sure if that level of detail was needed, though, given how absurd the story already was.
I don't think the key point for this particular story is actually that infection introduces more spike than vaccination. I don't think this phenomenon actually happens during infection, either. It might in some extreme cases, but I really don't think it's a real thing at all.
earlier tonight I was listening to twiv from the 16th, and they also covered this weird Spike protein paper. I really appreciate your write up, because it took them about half an hour or to explain but the reason they were covering something for which they were scratching their heads as to why the experiment was done in the first place given that it had no relation to anything real life was because anti-vaxxers were latching on to it.
I am now going to disregard my own advice about MDPI and ask you, John, if you have any thoughts on this ostensible report of a case of vaccine-induced MIS-C: https://www.researchgate.net/publication/356384174_Autoantibody_Release_in_Children_after_Corona_Virus_mRNA_Vaccination_A_Risk_Factor_of_Multisystem_Inflammatory_Syndrome
I see nothing in this case report connecting the inflammatory symptoms in this person (an 18 year old man who is for some reason described as a "boy") have anything to do with vaccination. 10 weeks from vaccination until the appearance of symptoms? Come on. That would mean that out of >1 billion people who have received mRNA vaccines at this point, this is the first person to have a new symptom more than 6 weeks after vaccination.
The much more likely scenarios are either (1) MIS-C is a misdiagnosis or (2) the COVID-19 negative test was a false negative. I find it odd that the case report is lacking in detail, too--they say he presented only with a fever, but was given antibiotics for "suspected pneumonia"? Was the stethoscope not available that day? The treating physician must have had more reason than simple temperature to begin empirical treatment.
This means that (1) has a lot of options here; generalized and unexplained inflammation along with suspected pneumonia? This sounds like a situation where this patient experienced an infection, and that infection led to all of these symptoms in some way or another. I do not see any reason to connect this with a vaccination that occurred 2.5 months earlier when nothing like that has ever happened to anyone else who got this vaccination.
Given that COVID-19 is everywhere, (2) is also a strong possibility.
The idea that the most likely explanation is a connection with the vaccine is just ludicrous.
An 18-year-old is by legal definition an adult. Therefore, he couldn't have MIS-C (defined as affecting a child), though he could have MIS-A.
Signed, the guy who owns nitpicking.com.
CDC definition also calls the border line for MIS-C the age of 21, but I think the term "boy" is rather inappropriate here. "Adolescent" might have been OK.
Eh, the WHO definition covers ages 0-19. Maybe time to just start calling it MIS?
Interestingly, though near-totally unrelatedly, in Germany (where this case report originated), the justice system treats people are juveniles until age 25.
How do nonsense conclusions like this pass peer review? This isn't the first egregiously overstepping conclusion I've seen by far, but it's probably one of the worst.
Well, let me tell you a story. I was in a lab once that was a regular peer reviewing lab for oncology papers. One day a paper came in that the PI decided wasn't worth his time, and he said he was going to send back a bad review unless his senior postdoc disagreed with his thinking that the paper was half-baked and under-developed. This was around 4 PM. The postdoc turned to me after the PI left and said, "Well, the future of this paper now depends on how tired I am today." Basically, the peer review process there was turning on a snap judgment and an exhausted and underpaid person.
I think of that story every time I see a problem with peer review, even though the situation is sort of opposite to what we see here. Peer reviewers are unpaid and overworked and sometimes--often?--come to hasty conclusions because they are not able to give the work they're assigned the attention that it is due.
However, the (academic) editor who worked on this is intended to be a second line of defense. Editors can ask for changes just as much as peer reviewers can. Editors should ask for changes to conclusions that are unsupported and likely to be inflammatory. Here, the editor didn't. I imagine because that person is underpaid, overworked, and wasn't paying great attention.
Academic publishing is pretty broken, because it grew out of a system of rich European nobles writing letters to each other, and hasn't become much more lucrative than how it started off. Peer review is a huge unpaid time sink, editing isn't much better, and despite enormous fees to publish and to subscribe, journals generally don't make very good margins. It's a problem to which I have no solutions, though I am sure there are smarter people than myself giving this attention.
MDPI has a reputation as a predatory publisher with an inadequate peer review process. They were on Jeffrey Beall's list of predatory publishers for a while; they were removed, but he later said this was due to pressure from his employer, and he continues to call them a predatory publisher elsewhere (e.g., on Twitter).
Now, a predatory journal is not quite the same thing as a pseudojournal, and I don't think anything appearing in an MDPI publication should necessarily be disregarded. Sometimes legit research appears on such publications because, e.g., the authors have been misled. But I do think such publishers in general, and MDPI in particular, have shown that what they publish warrants a higher-than-usual degree of scrutiny.
The first question I ask myself when these sorts of articles come out is: who are the authors? Do they actually have relevant expertise? Have they been active in peddling misinformation, conspiracies, pseudoscience?
I typically evaluate it based on the journal rather than the publisher, since there can be a lot of variation at the journal level. I've heard of Viruses before, and it has had some meaningfully valuable research in it before. This is not one of those cases.
Certainly going forward I'm going to be more skeptical than I was before.
That makes sense re: basing it on the journal rather than the publisher. In the case of Vaccines, though, I have to wonder whether the apparent far-right sympathies of MDPI's sole owner (see: https://forbetterscience.com/2020/12/29/mdpi-and-racism/) is playing a role here. (Anti-vaccine sentiment isn't the exclusive province of the far right, of course, but I think it's fair to say the two have found some... synergy during the pandemic.)
Did you see Respectful Insolence take down the paper?
https://respectfulinsolence.com/2021/11/17/does-spike-protein-from-covid-19-vaccines-interfere-with-dna-damage-repair/
Another article was just published, also from an MDPI journal, raising concerns about COVID vaccination in pregnancy: https://mdpi-res.com/d_attachment/vaccines/vaccines-09-01351/article_deploy/vaccines-09-01351.pdf
At least a couple of the authors have been involved in antivax activity in Canada.
Yeah, this paper I have heard of before. It is highly suspect and there have been retraction calls. The journal Vaccines has had a surprising number of these nonsensical antivaccine papers during the pandemic. This is one of the situations where I must look at the journal and say that it's not a good one.
You wrote, "Lastly, it just doesn’t seem possible for spike protein to be getting into the right place to do this. The mRNA and adenovirus-vector vaccines are all sent right into the muscle. They don’t go anywhere near the bone marrow and they don’t produce spike proteins in a way that it seems possible for those products to get into bone marrow or the thymus."
How about the non-US-approved vaccines, e. g. all the Chinese ones, that are either inactivated virus or protein subunit? I'm actually pretty sure neither one could introduce spike into the nucleus (where DNA replicates in mammalian cells) but you're the expert. Certainly spike can bind to the cell membrane, but does it pass the nuclear membrane?
You refer to a "protected compartment" (meaning the bone marrow), but at the cellular level the nucleus is also a protected compartment.
I think the key point is that infection introduces orders of magnitude more spike protein into a person's body than any vaccination, attached to actual virions.
The nuclear localization issue is pretty weird, I will agree with you. It's a bit of a head-scratcher. I have never heard anything about spike having a nuclear localization signal in its sequence. I don't know how it would get into the nucleus, either. I wasn't sure if that level of detail was needed, though, given how absurd the story already was.
I don't think the key point for this particular story is actually that infection introduces more spike than vaccination. I don't think this phenomenon actually happens during infection, either. It might in some extreme cases, but I really don't think it's a real thing at all.
Thanks.
We missed you at Philcon, by the way.